Repository logo

LSD alters dynamic integration and segregation in the human brain.

Accepted version

No Thumbnail Available



Change log


Luppi, Andrea I 
Carhart-Harris, Robin L 
Roseman, Leor 
Pappas, Ioannis 
Menon, David K 


Investigating changes in brain function induced by mind-altering substances such as LSD is a powerful method for interrogating and understanding how mind interfaces with brain, by connecting novel psychological phenomena with their neurobiological correlates. LSD is known to increase measures of brain complexity, potentially reflecting a neurobiological correlate of the especially rich phenomenological content of psychedelic-induced experiences. Yet although the subjective stream of consciousness is a constant ebb and flow, no studies to date have investigated how LSD influences the dynamics of functional connectivity in the human brain. Focusing on the two fundamental network properties of integration and segregation, here we combined graph theory and dynamic functional connectivity from resting-state functional MRI to examine time-resolved effects of LSD on brain networks properties and subjective experiences. Our main finding is that the effects of LSD on brain function and subjective experience are non-uniform in time: LSD makes globally segregated sub-states of dynamic functional connectivity more complex, and weakens the relationship between functional and anatomical connectivity. On a regional level, LSD reduces functional connectivity of the anterior medial prefrontal cortex, specifically during states of high segregation. Time-specific effects were correlated with different aspects of subjective experiences; in particular, ego dissolution was predicted by increased small-world organisation during a state of high global integration. These results reveal a more nuanced, temporally-specific picture of altered brain connectivity and complexity under psychedelics than has previously been reported.



Complexity, FMRI dynamics, Integration-segregation, LSD, Small-world network, Structure-function, Brain, Brain Mapping, Female, Hallucinogens, Humans, Image Processing, Computer-Assisted, Lysergic Acid Diethylamide, Magnetic Resonance Imaging, Male, Nerve Net, Neural Pathways

Journal Title


Conference Name

Journal ISSN


Volume Title



Elsevier BV


All rights reserved
Department of Health (via National Institute for Health Research (NIHR)) (unknown)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Royal College of Anaesthetists (RCoA) (unknown)
Medical Research Council (MR/M009041/1)
This work was supported by a Gates Cambridge Trust Scholarship [to AIL]; the Canadian Institute for Advanced Research (CIFAR) [to D.K.M. and E.A.S.]; the Cambridge Biomedical Research Centre and NIHR Senior Investigator Awards [to DKM], the Stephen Erskine Fellowship at Queens’ College, Cambridge [to EAS], the British Oxygen Professorship of the Royal College of Anaesthetists [to DKM]; the Imperial College President’s Scholarship [to L.R.]; the Oon Khye Beng Ch'Hia Tsio Studentship for Research in Preventive Medicine, administered via Downing College, University of Cambridge [to IP]. RLC-H is supported by the Alex Mosley Charitable Trust and supporters of the Centre for Psychedelic Research: The original study received support from a Crowd Funding Campaign and the Beckley Foundation, as part of the Beckley-Imperial Research Programme. Computing infrastructure at the Wolfson Brain Imaging Centre (WBIC-HPHI) was funded by the MRC research infrastructure award (MR/M009041/1). Data were provided in part by the Human Connectome Project, WU-Minn Consortium (Principal Investigators: David Van Essen and Kamil Ugurbil; 1U54MH091657) funded by the 16 NIH Institutes and Centers that support the NIH Blueprint for Neuroscience Research; and by the McDonnell Center for Systems Neuroscience at Washington University.